CN110025651A - A kind of compound celery oil self-emulsifying soft capsule and preparation method thereof with anti-aging effects - Google Patents

Abstract

The invention discloses a composite celery seed oil self-emulsifying soft capsule with anti-aging effect and a preparation method thereof. The preparation comprises celery seed oil, a compound vegetable oil with anti-aging effect and or can significantly enhance the anti-aging effect of celery seed oil, a homogeneous transparent solution made of surfactant, co-surfactant and other drugs. The invention utilizes that under suitable temperature conditions, the volatile celery seed oil is compounded with the vegetable oil that is not volatile and has anti-aging or can significantly enhance its effect to form a compound celery seed oil. medicines and or other medicines are made into soft capsules. The present invention can obtain a stable self-emulsifying system of celery seed oil or compound celery seed oil, which can improve the bioavailability of compound celery seed oil or celery seed oil and other medicines, and has quick onset of action and overcomes the problem of The disadvantages of common preparations of celery seed oil are low bioavailability and volatile, which significantly enhances the anti-aging effect of celery seed oil.

Description

A kind of compound celery seed oil self-emulsifying soft capsule with anti-aging effect and preparation thereof method

technical field

The invention belongs to the technical field of medicine, and in particular relates to a self-emulsifying soft capsule of celery seed oil or compound celery seed oil with anti-aging effect and a preparation method thereof.

Background technique

Celery seed oil is a hydrophobic yellow-green translucent oil extracted from celery seeds. Celery seed is the seed of celery (Apium graveolens L.). Celery is an annual or biennial herb and is cultivated all over the world. Celery not only has high edible value, but the oily substance extracted from its fruit is a yellow-green translucent oily liquid with a unique fresh aroma, which can be used as a seasoning spice in seasoning. Products, medicine, cosmetics and other fields are widely used. Celery seed oil is different from general vegetable seed oil. In addition to the fatty acid components contained in general vegetable seed oil, celery seed oil also contains a large amount of volatile oil (ie celery seed essential oil). ); At the same time, celery seed oil also contains chlorogenic acid (Chlorogenic Acid), caffeic acid, glycerol acid and other organic acids as well as flavonoids, butylphthalide, amino acids, dietary fiber, coumarin derivatives and many other substances. Modern pharmacological studies have shown that celery seed oil has good biological activities such as antioxidant, anti-tumor, bacteriostatic and insecticidal. Celery seeds are mainly used in Uyghur medicines to treat diseases such as hypertension, arthritis, rheumatoid arthritis, qi stagnation metritis, ascites, kidneys and other diseases. So far, the pharmacological research on lowering blood lipids has also been preliminarily explored. In recent years, celery seeds have been It is more and more concerned by people because of its rich nutrition and unique pharmacological properties.

Peony seed oil is a hydrophobic golden yellow transparent oil extracted from the seeds of Paeonia suffruticosa Andr. 93%, of which α-linolenic acid content is 42-67%; Perilla seed oil is a hydrophobic oil extracted from the seeds of Perilla frutescens L Brit. The total unsaturated fatty acids in perilla seed oil account for 90% of the fat content, of which α-linolenic acid content is 50 to 62%; A hydrophobic oily substance extracted, the total unsaturated fatty acids in Eucommia ulmoides seed oil account for 92% of the fat content, of which the content of α-linolenic acid is 50-66%; L.) seeds - a hydrophobic oily substance extracted from flaxseed, the total unsaturated fatty acids in flaxseed oil account for 91% of the fat content, of which the content of α-linolenic acid reaches 54-58%; Fruit oil is a hydrophobic oil extracted from Euphorbia volubilis (Plukenetia volubilis L., Inca Peanut, sachainchi). The content of α-linolenic acid is 46-53%. Peony seed oil, perilla seed oil, eucommia seed oil, linseed oil, and eucommia oil have a common feature in addition to their respective functions and characteristics: the proportion of total unsaturated fatty acids is high, all above 90%, of which α -The content of linolenic acid is much higher than other general vegetable oils. Alpha-linolenic acid has strong antioxidant activity and is an omega-3 unsaturated fatty acid. It is an essential fatty acid for the human body and constitutes the basic substance of cell membranes and biological enzymes. It plays an important role in antithrombotic and cancer prevention.

At present, celery seed oil on the market is mainly used as a spice in condiments, cosmetics and other fields because of its unique fresh aroma; there are relatively few researches in medicine, health food and food, and its invention patents are mainly concentrated on celery seed oil On the preparation method, such as Chinese patent CN 201510679016.4 discloses "a method of microwave-assisted low-temperature pressing of celery seed oil", and Chinese patent CN 201310276117.8 discloses "a method for enrichment and separation of celery seed oil" ”, as Chinese patent CN 201310144572.2 again discloses “a kind of molecular distillation and purification method of celery seed oil and its device”, also as Chinese patent CN201510215274.7 discloses “ a kind of celery seed oil extraction method”, adopts The combined extraction of celery seed oil by pressing and leaching process; no combination of celery seed oil with peony seed oil, perilla seed oil, eucommia seed oil, linseed oil, and quince fruit oil has been found to form a compound celery seed oil for anti-inflammatory drugs. The effect of aging, let alone celery seed oil combined with peony seed oil, perilla seed oil, eucommia seed oil, linseed oil, and quince fruit oil to form a compound celery seed oil to prepare a compound celery seed with anti-aging effect Oil self-emulsifying soft capsule and preparation method thereof. In addition to their respective nutritional values and functions, peony seed oil, perilla seed oil, eucommia seed oil, linseed oil, and eucommia oil have been found to have antioxidant, thrombosis-inhibiting, and blood-vessel-softening effects, respectively. The compatible use of seed oil can give full play to and improve the anti-aging effect of celery seed oil.

Celery seed oil is different from general vegetable seed oil, which mainly contains fatty acids and is not volatile. In addition to certain fatty acids, celery seed oil also contains a large amount of volatile terpenoids. In the process of preparation, attention should be paid to the volatility of celery seed oil. Therefore, the common preparation of celery seed oil and its self-emulsifying softener Compared with the capsule preparation, not only its bioavailability is relatively low, but also the volatile problem of celery seed oil is difficult to solve. The invention can not only obtain a stable celery seed oil self-emulsifying soft capsule preparation, but also improve the celery seed oil or the peony seed oil, perilla seed oil, eucommia seed oil and linseed oil matched with the celery seed oil. , The bioavailability of Meteng oil, fast onset. It overcomes the shortcomings of low bioavailability of common preparations of celery seed oil and its matching peony seed oil, perilla seed oil, eucommia seed oil, linseed oil, and quince fruit oil, and significantly enhances the anti-aging effect of celery seed oil. Moreover, the compound celery seed oil is formed by matching the celery seed oil with it, which can effectively overcome the volatile problem of the celery seed oil. At the same time, as a new combination formulation of celery seed oil, this product can provide consumers with a new choice.

SUMMARY OF THE INVENTION

The purpose of the present invention is to address the above-mentioned problems, to provide a self-emulsifying soft capsule of composite celery seed oil with anti-aging effect that has high bioavailability, is safe and convenient to take and can be significantly enhanced.

Another object of the present invention is to provide a preparation method of the above-mentioned self-emulsifying soft capsule preparation.

For achieving the above object, the technical scheme adopted in the present invention is:

A composite celery seed oil self-emulsifying soft capsule with anti-aging effect, comprising a capsule core and a capsule shell, wherein the capsule core is composed of the following components by weight: 39% to 74.5% of the composite celery seed oil, surface active 20 to 55% of surfactant, 5 to 20% of co-surfactant, and 0.5% to 1.0% of antioxidant.

In the above-mentioned compound celery seed oil self-emulsifying soft capsule with anti-aging effect, the compound celery seed oil is made up of celery seed oil and other vegetable oils, and other vegetable oils are selected from peony seed oil, perilla seed oil, Eucommia ulmoides Seed oil, flaxseed oil, cannabis oil.

In the above-mentioned composite celery seed oil self-emulsifying soft capsule with anti-aging effect, the weight composition ratio of the composite celery seed oil is: celery seed oil: peony seed oil=1:0.5-9.0 or celery seed oil Oil: Perilla Seed Oil = 1:0.5~9.0 or Celery Seed Oil: Eucommia Seed Oil = 1:0.5~9.0 or Celery Seed Oil: Flaxseed Oil = 1:0.5~9.0 or Celery Seed Oil: Mito Fruit oil=1:0.5～9.0;

Or celery seed oil: peony seed oil: perilla seed oil = 1: 0.5~4.5: 0.5~4.5 or celery seed oil: peony seed oil: eucommia seed oil = 1: 0.5~4.5: 0.5~4.5 or celery Seed oil: peony seed oil: linseed oil = 1: 0.5~4.5: 0.5~4.5 or celery seed oil: peony seed oil: quince oil = 1: 0.5~4.5: 0.5~ 4.5 or celery seed oil: Perilla seed oil: Eucommia seed oil = 1: 0.5~4.5: 0.5~4.5 or celery seed oil: perilla seed oil: linseed oil = 1: 0.5~4.5: 0.5~4.5 or celery seed oil: perilla Seed oil: Mito oil = 1:0.5~4.5:0.5~4.5 or Celery seed oil: Eucommia seed oil: Flaxseed oil = 1:0.5~4.5:0.5~4.5 or Celery seed oil: Eucommia seed oil: Meteng fruit oil = 1:0.5~4.5:0.5~4.5 or celery seed oil: linseed oil: Metten fruit oil = 1:0.5~4.5:0.5~4.5;

Or celery seed oil: peony seed oil: perilla seed oil: eucommia seed oil = 1: 0.5 to 3.0: 0.5 to 3.0: 0.5 to 3.0 or celery seed oil: peony seed oil: perilla seed oil: linseed oil ＝1:0.5～3.0:0.5～3.0:0.5～3.0 or Celery Seed Oil:Peony Seed Oil:Perilla Seed Oil:Meteng Fruit Oil=1:0.5～3.0:0.5～3.0:0.5～3.0 or Celery Seed oil: peony seed oil: eucommia seed oil: linseed oil = 1: 0.5~3.0: 0.5~3.0: 0.5~ 3.0 or celery seed oil: peony seed oil: eucommia seed oil: eucommia seed oil = 1: 0.5 ~ 3.0: 0.5 ~ 3.0: 0.5 ~ 3.0 or celery seed oil: peony seed oil: quince oil: flaxseed oil = 1: 0.5 ~ 3.0: 0.5 ~ 3.0: 0.5 ~ 3.0 or celery seed oil: perilla Seed oil: Eucommia seed oil: Flaxseed oil = 1:0.5~3.0:0.5~3.0:0.5~3.0 or Celery seed oil: Perilla seed oil: Flaxseed oil: Metten oil = 1:0.5~3.0: 0.5 to 3.0: 0.5 to 3.0 or celery seed oil: eucommia seed oil: linseed oil: eucalyptus oil = 1: 0.5 to 3.0: 0.5 to 3.0: 0.5 to 3.0 or celery seed oil: perilla seed oil: Eucommia ulmoides seed oil: Meiteng fruit oil=1:0.5～3.0:0.5～3.0:0.5～3.0;

Or celery seed oil: peony seed oil: perilla seed oil: eucommia seed oil: linseed oil = 1: 0.5～2.5: 0.5～2.5: 0.5～2.5: 0.5～2.5 or celery seed oil: peony seed oil: Perilla seed oil: Eucommia ulmoides seed oil: Metten fruit oil=1:0.5～2.5:0.5～2.5:0.5～2.5:0.5～2.5;

Or Celery Seed Oil: Peony Seed Oil: Perilla Seed Oil: Eucommia Seed Oil: Flaxseed Oil: Mito Oil = 1:0.5～1.5:0.5～1.5:0.5～1.5:0.5～1.5:0.5～1.5

In the above-mentioned composite celery seed oil self-emulsifying soft capsule with anti-aging effect, the preparation method of the composite celery seed oil is as follows: taking the celery seed oil and adding it to the ingredient container, and under the condition of 20～40 ℃, Add other vegetable oils, stir at slow speed for 20 to 30 minutes, and filter to obtain compound celery seed oil.

In the above-mentioned compound celery seed oil self-emulsifying soft capsule with anti-aging effect, in the self-emulsifying system, celery seed oil or compound celery seed oil is both an active ingredient or a main active ingredient or a medicine, and an oil phase , can also be a dispersant or diluent.

In the above-mentioned composite celery seed oil self-emulsifying soft capsule with anti-aging effect, the surfactant is selected from one of the following or their combination: soybean lecithin, egg yolk lecithin, liquid lecithin, and cephalin.

In the above-mentioned composite celery seed oil self-emulsifying soft capsule with anti-aging effect, the co-surfactant is selected from one of the following or their combination: glycerin, isopropanol, 1,2-propylene glycol, ethylene glycol Alcohol, ethanol, polyoxyethylene fatty acid ester or polyethylene glycol 400.

In the above-mentioned composite celery seed oil self-emulsifying soft capsule with anti-aging effect, the antioxidant is selected from one of the following or a combination thereof: vitamin E, vitamin C.

The above-mentioned preparation method of the composite celery seed oil self-emulsifying soft capsule with anti-aging effect, comprises the steps:

(1) Take the compound celery seed oil, add surfactant, co-surfactant and antioxidant at the temperature of 20-60 °C, stir well and filter to obtain a capsule core self-emulsifying system;

(2) Add the gelatin into the sol tank, add water at 60-80°C, add preservatives, seal and heat at the same time, stir until the melting and swelling are complete, add glycerin, seal the mixing tank, close the stirring, turn on the vacuum pump, vacuumize, and wait for the bubbles to be drawn. After cleaning, the soft capsule shell liquid is obtained, which is kept at 50-70° C. for later use.

(3) Take the soft capsule shell liquid and capsule core self-emulsifying system, put it on the soft capsule machine, and prepare the soft capsule by pressing method. After drying, washing, drying again, sorting and packaging, the finished product is obtained.

Compared with the common anti-aging celery seed oil preparation, the composite celery seed oil self-emulsifying soft capsule of the present invention can significantly enhance the anti-aging effect of the celery seed oil. It can be applied to the preparation of celery seed oil compound celery seed oil food, health food or medicine.

Based on the principle that celery seed oil and the compound celery seed oil composed of celery seed oil and selected vegetable seed oil are oil substances, they can play the role of oil phase themselves. They are not only active ingredients of APIs, but also oil Complementary materials. In particular the selected vegetable seed oil peony seed oil, or perilla seed oil, or eucommia seed oil, or linseed oil, or quince fruit oil, or peony seed oil and perilla seed oil and eucommia seed The oil and the vegetable seed oil complex composed of linseed oil and cannabis oil in any combination with each other, there are two other uses. One is to disperse or dissolve celery seed oil as a dispersing agent or carrier, so that the celery seed oil is relatively stable and less volatile; Active ingredient of API. Therefore, the present invention provides a new preparation of celery seed oil-compound celery seed oil self-emulsifying soft capsule preparation, which can significantly enhance the anti-aging effect of celery seed oil or compound celery seed oil, which is more efficient than the current market. The products sold have remarkable stability. At the same time, the present invention provides an option that provides a new safety product as an alternative to the existing technology.

In order to illustrate the beneficial effect of the compound celery seed oil fat emulsion preparation on the anti-aging effect, the present invention selects healthy Wistar rats as the research object, and is divided into 5 groups, namely the negative control group, the model control group, and the celery seed oil self-emulsifying soft Capsule preparation group, compound celery seed oil self-emulsifying soft capsule preparation group 1, compound celery seed oil self-emulsifying soft capsule preparation group 2. By observing the improvement of celery seed oil and compound celery seed oil self-emulsifying soft capsules on learning and memory of aging model animals, and comparing the content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in the brain tissue of aging animals The differences were summarized and the conclusions were summarized through statistical differences. The results showed that the compound celery seed oil self-emulsifying soft capsule preparation had a significant improvement effect on the aging indicators of aging model animals.

Compared with the prior art, the present invention has the following beneficial effects:

(1) The compound celery seed oil self-emulsifying soft capsule obtained by the present invention has high dispersibility, excellent storage stability, and especially the volatility of celery seed oil is suppressed due to compound compatibility with other selected vegetable seed oils, which overcomes existing problems. There are some defects of celery seed oil product, its bioavailability is greatly improved, and the medicinal effect of compound celery seed oil is improved.

(2) The composite celery seed oil itself of the present invention is an oil substance, which is not only an active ingredient of a crude drug, but also an oil phase auxiliary material, and other vegetable oils selected can be used as a dispersant or a carrier of the celery seed oil to disperse or dissolve the celery seed. The active ingredient of oil can also be used as an active ingredient of raw materials for anti-aging or auxiliary anti-aging effects; the self-emulsifying system formed by it can relatively increase the concentration of the drug in the self-emulsifying system, reduce the amount of self-emulsifying agent, and highlight the self-emulsifying system. The effect of emulsification.

(3) Compared with the existing common self-emulsifying soft capsule, the compound celery seed oil self-emulsifying soft capsule obtained by the present invention has reduced the part of medicine or oil phase, dispersing agent or carrier part, and the dosage of emulsifier and co-emulsifier is relatively small, and the dosage of dosage is relatively small. Relatively reduced, maximizing the efficacy of the active ingredients.

(4) The composite celery seed oil self-emulsifying soft capsule of the present invention combines volatile celery seed oil with non-volatile vegetable oil, thereby effectively increasing the stability of celery seed oil. The prepared self-emulsifying soft capsule can cover the bad smell of the medicine, has a good taste and is convenient to take.

(5) In the composite celery seed oil self-emulsifying soft capsule of the present invention, the selected main component celery seed oil is volatile, and by selecting peony seed oil, perilla seed oil, eucommia seed oil, linseed oil, and eucalyptus seed oil, respectively or Combining each other with celery seed oil can play a four-fold role: ① dispersing or dissolving celery seed oil and its active components; ② reducing the volatility of celery seed oil and its active components, and stabilizing the effect of celery seed oil; ③ It has anti-aging effect or auxiliary anti-aging effect; ④ It can be regarded as a component of the active ingredient of the API, and can be regarded as a component of the excipient.

(6) The emulsifier and co-emulsifier selected by the present invention are widely used pharmaceutical excipients in pharmacy, and have the characteristics of non-toxic and non-irritating. It not only solves the problem of bioavailability of oil components, but also does not increase the toxic and side effects of products.

(7) The method provided by the present invention has the advantages of simple technological process, convenient operation, convenient product quality control and operability, and is a safe and reliable preparation method suitable for industrial production.

Detailed ways

Embodiment 1: compound celery seed oil self-emulsifying soft capsule preparation one

1. The composition of ingredients is shown in Table 1:

Table 1 Composition of compound celery seed oil self-emulsifying soft capsules 1

2. Preparation method

(1) Blending of compound celery seed oil: Take celery seed oil as shown in Table 1, add it to the batching container, under the condition of 35 ℃, add peony seed oil, perilla seed oil, and vitamin E in turn, and stir slowly for 25 minutes. minutes, and filtered to obtain compound celery seed oil.

(2) As shown in Table 1, mix soybean lecithin and glycerin, use a shearing machine (8000 rpm), stir for two times, the first time is 5 minutes, and the second time is 2 minutes to make it evenly dispersed, add warm heat The compound celery seed oil is stirred 3 times for 5 minutes each time, and filtered to form a homogeneous liquid, that is, the self-emulsifying system of compound celery seed oil.

(3) As shown in Table 1, add gelatin into the sol tank, add water at 60°C, add preservative ethyl paraben, add sunscreen and colorant if necessary, seal and heat at the same time, stir until melting and swelling are complete, add glycerin , Close the mixing tank, turn off the stirring, turn on the vacuum pump, vacuumize, and remove the bubbles to obtain the soft capsule material liquid. Incubate at 50°C for later use.

(4) Take the soft capsule material liquid and compound celery seed oil self-emulsifying system on a soft capsule machine, prepare soft capsules by pressing method, dry, wash, re-dry, sort and pack to get the finished product.

3. Self-emulsifying effect detection

Take 0.5ml of the self-emulsifying system of the compound celery seed oil, add it to 10ml artificial gastric juice, and gently stir with a glass rod to quickly form an emulsion with blue opalescence. The particle size of the emulsion is measured with a TSM ultrafine particle size analyzer, and the result of the measurement is that the average particle size of the emulsion droplets is about 0.15 μm.

Embodiment 2: compound celery seed oil self-emulsifying soft capsule preparation two

1. The composition of ingredients is shown in Table 2:

Table 2 Composition of compound celery seed oil self-emulsifying soft capsule composition 2

2. Preparation method

(1) Blending of compound celery seed oil: Take celery seed oil as shown in Table 2, add it to the ingredient container, and under the condition of 35 ° C, add Eucommia seed oil, perilla seed oil, vitamin E, vitamin C in turn, slowly Blend at high speed for 20 minutes and filter to obtain complex celery seed oil.

(2) As shown in Table 2, take egg yolk lecithin, ethanol, and glycerin and mix, with shearing machine (8000 rpm), stir twice, the first time is 5 minutes, the second time is 2 minutes, make it dispersed evenly, add The warm compound celery seed oil is stirred 3 times for 5 minutes each time, and filtered to form a homogeneous liquid, that is, the self-emulsifying system of compound celery seed oil.

(3) As shown in Table 2, add gelatin into the sol tank, add water at 60°C, add preservative ethyl paraben, add sunscreen and colorant if necessary, seal and heat at the same time, stir until melting and swelling are complete, add glycerin , Close the mixing tank, turn off the stirring, turn on the vacuum pump, vacuumize, and remove the bubbles to obtain the soft capsule material liquid. Incubate at 50°C for later use.

(4) Take the self-emulsifying system of the soft capsule material liquid and compound celery seed oil, put the soft capsule machine on the soft capsule machine and prepare the soft capsule by pressing method. After drying, washing, drying, sorting and packaging, the finished product is obtained.

3. Self-emulsifying effect detection

Take 0.5ml of the self-emulsifying system of the compound celery seed oil, add it to 10ml artificial gastric juice, and gently stir with a glass rod to quickly form an emulsion with blue opalescence. The particle size of the emulsion was measured with a TSM ultrafine particle size analyzer, and the result of the measurement was that the average particle size of the emulsion droplets was about 0.14 μm.

Embodiment 3: compound celery seed oil self-emulsifying soft capsule preparation three

1. The composition of ingredients is shown in Table 3:

Table 3 Composition 3 of compound celery seed oil self-emulsifying soft capsules

2. Preparation method

(1) Reconciliation of compound celery seed oil: take celery seed oil as shown in Table 3, add it to the ingredient container, and under the condition of 30 ° C, add perilla seed oil, Eucommia ulmoides seed oil, peony seed oil, vitamin E, Vitamin C, blended on slow speed for 25 minutes, filtered to obtain complex celery seed oil.

(2) As shown in Table 2, get liquid lecithin, ethanol, glycerin and mix, with shearing machine (8000 rpm), stir twice, the first time is 5 minutes, the second time is 2 minutes, make it dispersed evenly, add The warm compound celery seed oil is stirred 3 times for 5 minutes each time, and filtered to form a homogeneous liquid, that is, the self-emulsifying system of compound celery seed oil.

(3) As shown in Table 3, add gelatin into the sol tank, add water at 60°C, add preservative ethyl paraben, add sunscreen and colorant if necessary, seal and heat at the same time, stir until melting and swelling are complete, add glycerin , Close the mixing tank, turn off the stirring, turn on the vacuum pump, vacuumize, and remove the bubbles to obtain the soft capsule material liquid. Incubate at 50°C for later use.

(4) Take the self-emulsifying system of the soft capsule material liquid and compound celery seed oil, put the soft capsule machine on the soft capsule machine and prepare the soft capsule by pressing method. After drying, washing, drying, sorting and packaging, the finished product is obtained.

3. Self-emulsifying effect detection

Take 0.5ml of the self-emulsifying system of the compound celery seed oil, add it to 10ml artificial gastric juice, and gently stir with a glass rod to quickly form an emulsion with blue opalescence. The particle size of the emulsion was measured with a TSM ultrafine particle size analyzer, and the result of the measurement was that the average particle size of the emulsion droplets was about 0.17 μm.

Embodiment 4: compound celery seed oil self-emulsifying soft capsule preparation four

1. The composition of ingredients is shown in Table 4:

Table 4 Composition of compound celery seed oil self-emulsifying soft capsule composition 4

2. Preparation method

(1) Blending of compound celery seed oil: Take celery seed oil as shown in Table 4, add it to the ingredient container, and at 36°C, add perilla seed oil, Eucommia seed oil, peony seed oil, and linseed oil in turn. , vitamin E, stir at slow speed for 25 minutes, and filter to obtain compound celery seed oil.

(2) As shown in Table 4, take egg yolk lecithin, soybean lecithin, and glycerin, use a shearing machine (8000 rpm), stir twice, the first time is 5 minutes, and the second time is 2 minutes to make it evenly dispersed, Add the warm compound celery seed oil, stir three times for 2 minutes each time, and filter to form a uniform liquid, that is, a self-emulsifying system of compound celery seed oil.

(3) As shown in Table 4, add gelatin into the sol tank, add water at 60°C, add preservative ethyl paraben, add sunscreen and colorant if necessary, seal and heat at the same time, stir until melting and swelling are complete, add glycerin , Close the mixing tank, turn off the stirring, turn on the vacuum pump, vacuumize, and remove the bubbles to obtain the soft capsule material liquid. Incubate at 50°C for later use.

(4) Take the self-emulsifying system of the soft capsule material liquid and compound celery seed oil, put the soft capsule machine on the soft capsule machine and prepare the soft capsule by pressing method. After drying, washing, drying, sorting and packaging, the finished product is obtained.

3. Self-emulsifying effect detection

Take 0.5ml of the self-emulsifying system of the celery seed oil, add it to 10ml artificial gastric juice, and gently stir with a glass rod to quickly form an emulsion with blue opalescence. The particle size of the emulsion was measured with a TSM ultrafine particle size analyzer, and the result was that the average particle size of the emulsion droplets was about 0.16 μm.

Embodiment 5: compound celery seed oil self-emulsifying soft capsule preparation five

1. The composition of ingredients is shown in Table 5:

Table 5 Composition of compound celery seed oil self-emulsifying soft capsule composition 5

2. Preparation method

(1) Blending of compound celery seed oil: Take celery seed oil as shown in Table 4, add it to the ingredient container, and at 36°C, add perilla seed oil, Eucommia seed oil, peony seed oil, and linseed oil in turn. , Meiteng fruit oil, vitamin E, stir at slow speed for 25 minutes, and filter to obtain compound celery seed oil.

(2) As shown in Table 4, take egg yolk lecithin, soybean lecithin, and glycerin, use a shearing machine (8000 rpm), stir twice, the first time is 5 minutes, and the second time is 2 minutes to make it evenly dispersed, Add the warm compound celery seed oil, stir three times for 2 minutes each time, and filter to form a uniform liquid, that is, a self-emulsifying system of compound celery seed oil.

(3) As shown in Table 4, add gelatin into the sol tank, add water at 60°C, add preservative ethyl paraben, add sunscreen and colorant if necessary, seal and heat at the same time, stir until melting and swelling are complete, add glycerin , Close the mixing tank, turn off the stirring, turn on the vacuum pump, vacuumize, and remove the bubbles to obtain the soft capsule material liquid. Incubate at 50°C for later use.

(4) Take the self-emulsifying system of the soft capsule material liquid and compound celery seed oil, put the soft capsule machine on the soft capsule machine and prepare the soft capsule by pressing method. After drying, washing, drying, sorting and packaging, the finished product is obtained.

3. Self-emulsifying effect detection

Take 0.5ml of the self-emulsification system of the celery seed oil, add it to 10ml of artificial gastric juice, and gently stir with a glass rod to quickly form an emulsion with blue opalescence. The particle size of the emulsion was measured with a TSM ultrafine particle size analyzer, and the result of the measurement was that the average particle size of the emulsion droplets was about 0.13 μm.

Example 6: Study on the anti-aging effect of compound celery seed oil self-emulsifying soft capsules on aging model rats

The free radical theory of aging believes that aging is caused by excessive production of free radicals and causes lipid peroxidation, which damages biological membranes, proteins (enzymes) and genetic materials, and ultimately leads to aging. Reactive oxygen radicals (O ₂ ^- and H ₂ O ₂ ) scavenger superoxide dismutase (SOD) can scavenge toxic O ₂ ^- and H ₂ O ₂ by disproportionation and reduction, thereby preventing them from causing free radicals. The chain reaction reduces the formation of the free radical metabolite malondialdehyde (MDA). Therefore, SOD activity can be used as an important indicator of the body's resistance to aging. In addition, MDA can also be used as an indicator of antioxidant.

Celery seed oil is a hydrophobic yellow-green translucent oil extracted from celery seeds, containing flavonoids, chlorogenic acid, caffeic acid, glyceric acid, volatile oil, butylphthalide, coumarin celery seed oil can increase the activity of SOD in the body; peony seed oil, perilla seed oil, eucommia seed oil, linseed oil, and quince fruit oil are obtained from their respective plant seeds or fruits In addition to their respective functions and characteristics, the extracted special oils have a common feature: the proportion of total unsaturated fatty acids is high (both above 90%), and the content of α-linolenic acid is much higher than that of other general vegetable oils. can be as high as 60%. Alpha-linolenic acid has strong antioxidant activity and is an omega-3 unsaturated fatty acid. It is an essential fatty acid for the human body and plays an important role in anti-aging. Therefore, with celery seed oil as the main active ingredient, and/or peony seed oil, and/or perilla seed oil, and/or eucommia seed oil, and/or linseed oil, and/or quince oil The compound celery seed oil composed of the compound celery seed oil is prepared into a self-emulsifying soft capsule of the compound celery seed oil, which maximizes the anti-aging effect of the celery seed oil and has an unexpected effect. This experiment mainly studies the improvement of learning and memory impairment of aging animals by compound celery seed oil self-emulsifying soft capsules, reduces the content of MDA in the brain tissue of aging mice and increases the activity of SOD to observe the anti-aging effect of compound celery seed oil.

1 Experimental materials and methods

1.1 Materials and Reagents

1.1.1 Experimental reagents

Celery seed oil is prepared by the method of microwave-assisted low-temperature pressing in our company. The preparation method of celery seed oil is as follows: removing impurities and drying celery seeds→microwave treatment for 60-120s→pressing by a low temperature press→crude celery seed oil→centrifugation, filtering→celery seed oil.

Celery seed oil self-emulsifying soft capsules (self-emulsifying 1 system) were prepared according to the method of above-mentioned embodiment 1, the peony seed oil and perilla seed oil in embodiment 1 were replaced with equal amount of soybean oil, and celery seeds were compounded successively respectively. Oil self-emulsifying soft capsules are provided with 1 group of compound celery seed oil self-emulsifying soft capsule preparations and 2 groups of compound celery seed oil self-emulsifying soft capsule preparations prepared in Example 1 and Example 4, respectively named as self-emulsifying 1 System, self-emulsifying 2 systems, self-emulsifying 3 systems, namely self-emulsifying 1 system is celery seed oil self-emulsifying soft capsule, self-emulsifying 2 system is compound celery seed oil self-emulsifying soft capsule preparation 1 group (Embodiment 1), Self-emulsifying 3 system is compound celery seed oil self-emulsifying soft capsule preparation group 2 (Example 4).

Piracetam Tablets: Shandong Renhetang Pharmaceutical Co., Ltd.; D-Galactose: German Sigma Company; Superoxide Dismutase (SOD), Malondialdehyde (MDA), Total Protein, Nitric Oxide (NO), Nitric oxide synthase (NOS) assay kit: Shanghai Changjin Biotechnology Co., Ltd.; other reagents are of analytical grade.

1.1.2 Experimental instruments and equipment

Morris water maze system: Beijing Zhongshi Dichuang Technology Development Co., Ltd.; DY89-Ⅱ Electric Glass Homogenizer: Ningbo Xinzhi Biotechnology Co., Ltd.; HH-21-6 Electric Thermostatic Water Bath: Changzhou Nokia Instrument Co., Ltd. ; WH-1 Micro Vortex Mixer: Shanghai Huxi Analytical Instrument Factory Co., Ltd.; GTR16-2 high-speed refrigerated centrifuge: Beijing Times Beili Centrifuge Co., Ltd.; 752 UV-Vis Spectrophotometer: Shanghai Spectrum Instrument Co., Ltd.

1.1.3 Experimental animals

60 clean-grade Wistar rats, male, weighing 200 ± 20 g, were provided by the Guangdong Provincial Medical Laboratory Animal Center, and the animal quality certificate number: No.44411600000901. Laboratory animal license number: SYXK (Guangdong) 2013-0002. Breeding environment: SPF grade, single cage for raising.

1.2 Experimental method

1.2.1 Animal grouping, modeling and administration

(1) Animal grouping: 60 Wistar rats were fed for a week to adapt to the environment and randomly divided into 5 groups: negative control group, model group, self-emulsifying 1 system group, self-emulsifying 2 system group, and self-emulsifying 3 system Group.

(2) Modeling of aging model: Except for the negative control group, D-galactose was subcutaneously injected into the neck of the other groups every day. The dose of D-galactose is 125mg/kg, and the subcutaneous injection volume should be controlled at 0.2mL/100g. D-galactose solution preparation: 6.25g is dissolved in 100mL normal saline, and the subcutaneous injection volume can be controlled to be 0.2mL/100g. The negative control group was injected with the same volume of normal saline for 8 consecutive weeks. During the modeling process, the self-emulsifying system drugs were administered by gavage at the same time.

(3) Administration: According to the larger dose of celery seed oil per adult per day, the equivalent dose of about 0.6g/kg in rats is obtained by corresponding conversion, and the rats are given orally every day. Administration, administration for 8 weeks, the negative control group was given the same volume of self-emulsifying 1 system without celery seed oil. After the experiment, the weight-bearing swimming test and the water maze test were performed, during which the drug was continuously administered.

1.2.2 Weight-bearing swimming test experiment

For the weight-bearing swimming test experiment, a smooth drum with a diameter of 80cm and a height of 100cm was used. A lead strip was tied to the root of the rat's tail, and the mass was 10% of the rat's body weight. The time was started when the rat was put into the water. When the rat's head submerged in the water for more than 10s, the experiment was over and the time was recorded. The weight-bearing swimming test experiment mainly tests the anti-fatigue ability.

1.2.3 Morris water maze experiment

The Morris water maze is composed of a stainless steel circular water tank, a platform hidden below the water surface, and a set of automatic image acquisition and processing systems (cameras, displays, and analysis software, etc.). The inner diameter of the sink is 1.5m and the height is 0.5m. The circumference of the sink is smooth and the inner wall is painted black. The circular water tank was divided into 4 quadrants (Ⅰ, Ⅱ, Ⅲ and Ⅳ), and a mark was selected on the wall of the water tank in each of the four quadrants as the water entry point, and the rats were put into the water facing the wall of the water tank each time. The platform is located in the second quadrant, and the water surface should be 2cm higher than the platform. A video camera connected to the display system was installed above the water tank to record the rat movement trajectories synchronously. The light in the room is constant, and no light directly hits the sink. During the whole experiment, the reference objects around the water tank could not move, and the experimenter should not appear within the visual range of the animal, and kept quiet and no noise. One day before the experiment, rats in all groups swim freely and adapt to the water tank environment. The experiment lasted 5 days and was carried out in two stages:

(1) Positioning navigation experiment: Each rat was trained for 4 times, and then entered the water from the water entry points of the I, II, III and IV quadrants toward the tank wall. The time from entering the water to finding the platform was recorded, which was the escape latency (Escape latency). After the rat boarded the platform, let it stay on the platform for 15s. If the rat could not find the platform within 90 s, it was pulled to the platform, and it also stayed on the platform for 15 s, and the latency was recorded as 90 s. After each training, the rats were allowed to rest for 15 s, and the average of the latencies of the four quadrants was recorded as the escape latency of the day. The training was carried out for 4 days in total, and the escape latency on the 4th day was used as the final score to test the learning ability of the rats.

(2) Space exploration experiment: start the space search experiment on the 5th day, remove the underwater platform, put the rats into the water from the fourth quadrant entry point farthest from the original platform II quadrant, and record the rats within 90s The times of crossing the original platform position and the effective time ratio (ie the ratio of the swimming time in the quadrant where the original platform was located to the total swimming time) were used to test the memory ability of the rats.

1.2.4 Determination of biochemical indicators

The rats were killed by fasting for 12 hours after the last day of administration. They were sacrificed by decapitation, and blood was collected in a 15mL EP tube. The blood was centrifuged at room temperature for 30 minutes, centrifuged at 3000 r/min at 4°C for 10 minutes, and the upper serum was collected for the detection of superoxide dismutase (SOD) and malondialdehyde (MDA). The rat was killed by decapitation, the head of the rat was placed on an ice tray, the brain was quickly peeled off, rinsed with pre-cooled normal saline, a 10% tissue homogenate was prepared, centrifuged at 3000 r/min at 4 °C, the supernatant was taken, and the total amount of tissue was collected. Detection of protein, nitric oxide (NO), nitric oxide synthase (NOS).

1.2.5 Statistical methods

experimental data with Statistical software SPSS17.0 was used, one-way ANOVA was used for comparison among multiple groups, and t test was used for comparison between groups, and P<0.05 was considered statistically significant.

2 Experimental results

2.1 Weight-bearing swimming test results

The weight-bearing swimming test results are shown in Table 6. Compared with the model group, the weight-bearing swimming time of the negative control group was significantly longer than that of the model group (P<0.05), indicating that the aging model was successfully established; The swimming time of the emulsifying 2 system group and the self-emulsifying 3 system group was also significantly longer than that of the model group (P<0.05). The results show that both celery seed oil self-emulsifying soft capsules and compound celery seed oil self-emulsifying soft capsules can enhance the anti-fatigue ability of aging model rats, and the compound celery seed oil self-emulsifying soft capsules can resist fatigue in aging model rats. The ability is significantly enhanced than that of celery seed oil self-emulsifying softgels.

Table 6 Results of weight-bearing swimming test of rats in each group (n=12)

group swimming time/min negative control group 17.86±0.37^★ model group 11.12±0.29 Self Emulsifying 1 System Group 15.76±0.24^★ Self-emulsifying 2 system group 17.41±0.38^★ Self-emulsifying 3 system group 17.65±0.35^★

Note: Compared with the model group, ^★ P＜0.05, ^★★ P＜0.01.

2.2 Water maze results

The results of the water maze are shown in Table 7. Compared with the model group, the escape latency of the rats in the negative control group was significantly shorter than that in the model group (P<0.05), and the effective time ratio and the number of crossing the platform were significantly higher than those in the model group (P<0.05). Compared with the model group, the escape latency of each group of self-emulsifying soft capsules was significantly shorter than that of the model group (P<0.05), and the effective time ratio of the celery seed oil self-emulsifying soft capsule group was higher than that of the model group (P<0.05). ), the celery seed oil self-emulsifying soft capsule group had no significant difference in the times of crossing the platform, and the effective time ratio and crossing times of the celery seed oil self-emulsifying soft capsule group were significantly higher than those in the model group (P<0.05). The above results show that celery seed oil self-emulsifying soft capsules can enhance the learning and memory ability of aging model rats, and the effect of compound celery seed oil self-emulsifying soft capsules on the learning and memory ability of aging model rats is significantly stronger than that of celery seeds. Oil self-emulsifying softgels.

Table 7 Morris water maze test results of rats in each group (n=12)

group Incubation period/s Effective time ratio Number of crossing platforms negative control group 33.34±7.53^★ 0.3584±0.1528^★ 3.60±2.31^★ model group 52.01±6.06 0.3013±0.2212 2.01±1.47 Self Emulsifying 1 System Group 39.83±4.76^★ 0.3542±0.2101^★ 2.68±1.81 Self-emulsifying 2 system group 33.54±4.21^★ 0.3658±0.1987^★ 3.57±1.88^★ Self-emulsifying 3 system group 32.96±4.16^★ 0.3715±0.2209^★ 3.61±1.93^★

Note: Compared with the model group, ^★ P＜0.05, ^★★ P＜0.01.

2.3 Biochemical index results

The measurement results of serum biochemical indexes of rats are shown in Table 8. Compared with the model group, the SOD activity of the negative control group was significantly higher than that of the model group (P<0.05), and the MDA content was significantly lower than that of the model group (P<0.05). In comparison, the SOD activity of the celery seed oil self-emulsifying soft capsule group and the compound celery seed oil self-emulsifying soft capsule group were significantly higher than those of the model group (P<0.05), and the MDA content was significantly lower than that of the model group (P<0.05), and The vitality of the compound celery seed oil self-emulsifying soft capsule group was stronger than that of the celery seed oil self-emulsifying soft capsule group.

Table 8 Determination results of serum biochemical indexes of rats in each group

group SOD/(U/mL) MDA/(nmol/mL) negative control group 274.07±29.49^★ 4.78±0.34^★ model group 154.79±18.87 6.32±0.57 Self Emulsifying 1 System Group 261.24±45.37^★ 3.71±0.58^★ Self-emulsifying 2 system group 274.92±46.53^★ 2.96±0.45^★ Self-emulsifying 3 system group 275.93±23.56^★ 2.91±0.38^★

Note: Compared with the model group, ^★ P＜0.05, ^★★ P＜0.01.

3 Conclusions

The results of the modeling experiment show that the D-galactose subacute aging model replicated in this experiment is reliable; the results of the weight-bearing swimming experiment show that both celery seed oil self-emulsifying soft capsules and compound celery seed oil self-emulsifying soft capsules can enhance The anti-fatigue ability of aging model rats, and the anti-fatigue ability of compound celery seed oil self-emulsifying soft capsules on aging model rats is significantly enhanced than that of celery seed oil self-emulsifying soft capsules; Emulsifying soft capsules can enhance the learning and memory ability of aging model rats, and the effect of compound celery seed oil self-emulsifying soft capsules on the learning and memory ability of aging model rats is significantly stronger than that of celery seed oil self-emulsifying soft capsules; biochemical index determination The results showed that both celery seed oil self-emulsifying soft capsules and composite celery seed oil self-emulsifying soft capsules could increase the activity of superoxide dismutase, reduce the content of malondialdehyde in the body and scavenge free radicals in the body to protect the body.

The results of this experiment also show that not only celery seed oil self-emulsifying soft capsules and compound celery seed oil self-emulsifying soft capsules have good anti-aging effects, but also celery seed oil can be combined with peony seed oil and perilla seed oil. , Eucommia seed oil, linseed oil, and Metten fruit oil are compounded and prepared by self-emulsification to form compound celery seed oil self-emulsifying soft capsules, which obviously enhances the anti-aging effect of celery seed oil and achieves an ideal Effect.

Claims (8)

1. a kind of compound celery oil self-emulsifying soft capsule with anti-aging effects, including capsule-core and softgel shell, it is characterised in that The capsule-core is grouped as by the group of following weight percent: compound celery oil 39%~74.5%, and surfactant 20~ 55%, cosurfactant 5~20%, antioxidant 0.5%~1.0%.

2. as described in claim 1 with the compound celery oil self-emulsifying soft capsule of anti-aging effects, it is characterised in that institute It states compound celery oil to be made of celery oil and other plant oil, other plant oil is selected from peony seed oil, Purple Perilla Seed Oil, Cortex Eucommiae Seed oil, linseed oil, oil and fat of sacha inchi.

3. as claimed in claim 2 with the compound celery oil self-emulsifying soft capsule of anti-aging effects, it is characterised in that institute State the weight ratio of components of compound celery oil are as follows: celery oil: peony seed oil=1:0.5~9.0 or celery oil: Purple Perilla Seed Oil= 1:0.5~9.0 or celery oil: eucommia ulmoides seed oil=1:0.5~9.0 or celery oil: linseed oil=1:0.5~9.0 or celery Seed oil: oil and fat of sacha inchi=1:0.5~9.0；

Or celery oil: peony seed oil: Purple Perilla Seed Oil=1:0.5~4.5:0.5~4.5 or celery oil: peony seed oil: Du Secondary seed oil=1:0.5~4.5:0.5~4.5 or celery oil: peony seed oil: linseed oil=1:0.5~4.5:0.5~4.5 or Celery oil: peony seed oil: oil and fat of sacha inchi=1:0.5~4.5:0.5~4.5 or celery oil: Purple Perilla Seed Oil: eucommia ulmoides seed oil= 1:0.5~4.5:0.5~4.5 or celery oil: Purple Perilla Seed Oil: linseed oil=1:0.5~4.5:0.5~4.5 or celery seed Oil: Purple Perilla Seed Oil: oil and fat of sacha inchi=1:0.5~4.5:0.5~4.5 or celery oil: eucommia ulmoides seed oil: linseed oil=1:0.5 ~4.5:0.5~4.5 or celery oil: eucommia ulmoides seed oil: oil and fat of sacha inchi=1:0.5~4.5:0.5~4.5 or celery oil: sub- Flaxseed oil: oil and fat of sacha inchi=1:0.5~4.5:0.5~4.5；

Or celery oil: peony seed oil: Purple Perilla Seed Oil: eucommia ulmoides seed oil=1:0.5~3.0:0.5~3.0:0.5~3.0 or celery Seed oil: peony seed oil: Purple Perilla Seed Oil: linseed oil=1:0.5~3.0:0.5~3.0:0.5~3.0 or celery oil: peony seeds Oil: Purple Perilla Seed Oil: oil and fat of sacha inchi=1:0.5~3.0:0.5~3.0:0.5~3.0 or celery oil: peony seed oil: seed of bark of eucommia Oil: linseed oil=1:0.5~3.0:0.5~3.0:0.5~3.0 or celery oil: peony seed oil: eucommia ulmoides seed oil: oil and fat of sacha inchi =1:0.5~3.0:0.5~3.0:0.5~3.0 or celery oil: peony seed oil: oil and fat of sacha inchi: linseed oil=1:0.5~ 3.0:0.5~3.0:0.5~3.0 or celery oil: Purple Perilla Seed Oil: eucommia ulmoides seed oil: linseed oil=1:0.5~3.0:0.5~ 3.0:0.5~3.0 or celery oil: Purple Perilla Seed Oil: linseed oil: oil and fat of sacha inchi=1:0.5~3.0:0.5~3.0:0.5~ 3.0 or celery oil: eucommia ulmoides seed oil: linseed oil: oil and fat of sacha inchi=1:0.5~3.0:0.5~3.0:0.5~3.0 or celery Seed oil: Purple Perilla Seed Oil: eucommia ulmoides seed oil: oil and fat of sacha inchi=1:0.5~3.0:0.5~3.0:0.5~3.0；

Or celery oil: peony seed oil: Purple Perilla Seed Oil: eucommia ulmoides seed oil: linseed oil=1:0.5~2.5:0.5~2.5:0.5~ 2.5:0.5~2.5 or celery oil: peony seed oil: Purple Perilla Seed Oil: eucommia ulmoides seed oil: oil and fat of sacha inchi=1:0.5~2.5:0.5~ 2.5:0.5~2.5:0.5~2.5；

Or celery oil: peony seed oil: Purple Perilla Seed Oil: eucommia ulmoides seed oil: linseed oil: oil and fat of sacha inchi=1:0.5~1.5:0.5~ 1.5:0.5~1.5:0.5~1.5:0.5~1.5.

4. as described in claim 1 with the compound celery oil self-emulsifying soft capsule of anti-aging effects, it is characterised in that institute State compound celery oil the preparation method comprises the following steps: takes celery oil to be added in proportion container, and under conditions of 20~40 DEG C, it is added His vegetable oil, mixes slowly 20~30 minutes, compound celery oil is obtained after filtering.

5. as described in claim 1 with the compound celery oil self-emulsifying soft capsule of anti-aging effects, it is characterised in that institute The surfactant stated is selected from one of following or their combination: soybean lecithin, egg yolk lecithin, liquid lecithin, cephalin.

6. as described in claim 1 with the compound celery oil self-emulsifying soft capsule of anti-aging effects, it is characterised in that institute The cosurfactant stated is selected from one of following or their combination: glycerol, isopropanol, l, 2 one propylene glycol, ethylene glycol, ethyl alcohol, Polyoxyethylene fatty acid ester or polyethylene glycol 400.

7. as described in claim 1 with the compound celery oil self-emulsifying soft capsule of anti-aging effects, it is characterised in that institute The antioxidant stated is selected from one of following or their combination: vitamin E, vitamin C.

8. a kind of described in any item compound celery oil self-emulsifying soft capsules with anti-aging effects of claim 1-7 Preparation method, it is characterised in that include the following steps:

(1) compound celery oil is taken, under 20-60 DEG C of Conditions Temperature, surfactant, cosurfactant, antioxidant is added, It stirs, filters, obtain capsule-core self-emulsifying drug delivery systems；

(2) gelatin is added in glue pot, 60-80 DEG C of water is added, preservative is added, it is closed to heat simultaneously, it stirs molten to melting It is swollen that glycerol is added completely, it is closed to match glue tank, stirring is closed, vacuum pump is opened, vacuumizes, pump to bubble to get soft capsule Shell liquid, 50-70 DEG C of heat preservation are spare；

(3) soft capsule shell liquid, capsule-core self-emulsifying drug delivery systems are taken, and upper encapsulating machine prepares soft capsule using pressing, through drying, washes It washs, re-dry, sorting, packs, obtain finished product.